Stereoselective Synthesis of 1-Substituted Homotropanones, including Natural Alkaloid (-)-Adaline.

The stereocontrolled synthesis of 1-substituted homotropanones, using chiral --butanesulfinyl imines as reaction intermediates, is described. The reaction of organolithium and Grignard reagents with hydroxy Weinreb amides, chemoselective --butanesulfinyl aldimine formation from keto aldehydes, decarboxylative Mannich reaction with β-keto acids of these aldimines, and organocatalyzed L-proline intramolecular Mannich cyclization are key steps of this methodology. The utility of the method was demonstrated with a synthesis of the natural product (-)-adaline, and its enantiomer, (+)-adaline.